CHRONOFASTING: The Role of Chronotype in Treatment of Overweight/Obesity in Adolescence: The Study Protocol for a Randomized Controlled Trial

Childhood and adolescent obesity represents a major global public health concern, with a steadily increasing prevalence over recent decades, accompanied by a rise in metabolic disorders among younger populations. Time-restricted feeding (TRF) has emerged as a promising dietary intervention, with preliminary evidence suggesting potential beneficial effects on body weight reduction and metabolic parameters in adolescents with overweight or obesity.

Chronotype, defined as an individual's sleeping habits and daily activities, has a biological basis and is influenced by the circadian rhythm. Chronotype is shaped by behavioral and environmental factors, including sleep schedules, meal timing, and light exposure, and plays an important role in regulating physiological processes. Notably, adolescents with a late chronotype are more likely to exhibit higher body mass index (BMI), irregular eating patterns, including breakfast skipping, and potentially reduced responsiveness to weight-loss interventions.

Despite the growing body of literature on TRF in adolescents, existing intervention models remain heterogeneous and do not account for chronotype as a potential modifier of treatment effectiveness. This represents an important gap in current research.

Therefore, investigating the interaction between chronotype and the timing of food intake within TRF regimens is of particular interest. Additionally, comparing different intervention strategies with a control group may provide more robust evidence regarding their relative effectiveness.

The aim of this randomized controlled trial is to evaluate the effectiveness of two TRF interventions combined with calorie restriction on weight loss in adolescents with overweight or obesity and a late chronotype, compared with a control group receiving calorie restriction without specific instructions regarding meal timing.

The primary outcome variable is the change in body weight z-score, measured at baseline, at week 4, week 8 and at the end of the intervention (week 12). Secondary outcomes include changes in fat mass (FM), fat-free mass (FFM), waist circumference (WC), waist-to-hip ratio (WHR), handgrip strength, and behavioral outcomes, including physical activity levels (PAL), quality of life (QoL), and changes in chronotype.

Intercurrent events, such as non-adherence to the intervention, will be handled using an intention-to-treat approach, including all randomized participants in the analysis.

All participants will be monitored throughout the study period. Adherence to the intervention protocols will be assessed through CGM system and via 24 hour dietary recalls and monitoring of eating windows. Participants will be instructed to record daily meal timing, and adherence will be evaluated based on consistency with the prescribed time-restricted feeding schedule. Continuous glucose monitoring will be performed during the first and last 14 days of the study. All participants in the groups will be monitored. All participants will receive a phone call assessment in week 6 to ensure adherence

Participation in this study may provide potential benefits, including weight loss, improved metabolic health, and increased awareness of healthy lifestyle behaviors. Additionally, this study may contribute to the development of more effective and personalized dietary interventions for adolescent obesity.

Potential risks are expected to be minimal and primarily related to TRF, including temporary hunger, fatigue, or mild discomfort, particularly during the initial adaptation period, as well as mild irritation associated with CGM sensor placement. These effects are anticipated to be transient and will be carefully monitored throughout the study..